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41.
Tatsuya Yamashita Kuniaki Arai Akito Sakai Eishiro Mizukoshi Yoshio Sakai Takashi Kagaya Yasunari Nakamoto Masao Honda Takashi Wada Hitoshi Yokoyama Shuichi Kaneko 《Hepatology research》2006,36(3):167-175
PURPOSE: In patients with chronic genotype 1b hepatitis C and a high viral load, the viral load was reduced by double filtration plasmapheresis (DFPP), followed by combined interferon and ribavirin therapy. The safety and virological effects of this treatment method were preliminarily investigated. METHODS: In nine patients with chronic hepatitis C, DFPP was performed three times on days 1, 2, and 4, and the administration of interferon and ribavirin was initiated immediately after DFPP on day 1. RESULT: The HCV RNA was undetectable in all patients after the plasma was passed through a plasma fractionator (second filter) in the DFPP circuit. After 2 weeks, the HCV RNA tended to decrease in the DFPP group more than in the control group (-2.45+/-1.12 versus -1.57+/-0.95, P=0.073). However, this decrease was not attributable to a sustained virological response (SVR) (22.2% versus 18.2%, P=0.822). Most of the adverse events were caused by the interferon and ribavirin combination therapy. CONCLUSION: DFPP can be safely performed concomitantly with interferon and ribavirin combination therapy in chronic hepatitis C patients. The combination may contribute to an early virological response. The effect of DFPP on the SVR and its significance remain to be clarified. 相似文献
42.
Nobutoshi Komatsu Utaroh Motosugi Shinya Maekawa Kuniaki Shindo Minoru Sakamoto Mitsuaki Sato Akihisa Tatsumi Mika Miura Fumitake Amemiya Yasuhiro Nakayama Taisuke Inoue Mitsuharu Fukasawa Tomoyoshi Uetake Masahiko Ohtaka Tadashi Sato Yasuhiro Asahina Masayuki Kurosaki Namiki Izumi Tomoaki Ichikawa Tsutomu Araki Nobuyuki Enomoto 《Hepatology research》2014,44(13):1339-1346
43.
Hiroyasu Ito Tatsuya Ando Kazuki Ando Tetsuya Ishikawa Kuniaki Saito Hisataka Moriwaki Mitsuru Seishima 《Immunology》2014,142(4):614-623
Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in viral clearance during acute infections, including hepatitis B virus (HBV) infection. A persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV‐specific CTLs leads to the clearance of HBV in patients with a chronic HBV infection. Previously, we reported that α‐galactosylceramide (α‐GalCer), a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV surface antigen (HBsAg)‐specific CTLs. In the present study, we found that inhibition of indoleamine 2,3‐dioxygenase (IDO) activity enhanced the induction of HBsAg‐specific CTLs after immunization with HBsAg and α‐GalCer. The administration of HBsAg and α‐GalCer increased the production of interleukin‐2 and interleukin‐12b, which are crucial for the induction of HBsAg‐specific CTLs. The production of these cytokines was more strongly enhanced in IDO knockout mice compared with wild‐type mice. In addition, α‐GalCer induced the production of IDO in CD11b+ cells, and these cells inhibited proliferation of HBsAg‐specific CTLs. Our results lead to strategies for improving the induction of HBsAg‐specific CTLs. 相似文献
44.
Minghua Wu Yutaro Obara Ikuo Norota Yoshinobu Nagasawa Kuniaki Ishii 《Pflügers Archiv : European journal of physiology》2014,466(5):937-946
Abnormal QT prolongation in diabetic patients has become a clinical problem because it increases the risk of lethal ventricular arrhythmia. In an animal model of type 1 diabetes mellitus, several ion currents, including the slowly activating delayed rectifier potassium current (IKs), are altered. The IKs channel is composed of KCNQ1 and KCNE1 subunits, whose genetic mutations are well known to cause long QT syndrome. Although insulin is known to affect many physiological and pathophysiological events in the heart, acute effects of insulin on cardiac ion channels are poorly understood at present. This study was designed to investigate direct electrophysiological effects of insulin on IKs (KCNQ1/KCNE1) currents. KCNQ1 and KCNE1 were co-expressed in Xenopus oocytes, and whole cell currents were measured by a two-microelectrode voltage-clamp method. Acute application of insulin suppressed the KCNQ1/KCNE1 currents and phosphorylated Akt and extracellular signal-regulated kinase (ERK), the two major downstream effectors, in a concentration-dependent manner. Wortmannin (10?6 M), a phosphoinositide 3-kinase (PI3K) inhibitor, attenuated the suppression of the currents and phosphorylation of Akt by insulin, whereas U0126 (10?5 M), a mitogen-activated protein kinase kinase (MEK) inhibitor, had no effect on insulin-induced suppression of the currents. In addition, insulin had little effect on KCNQ1 currents without KCNE1, which indicated an essential role of KCNE1 in the acute suppressive effects of insulin. Mutagenesis studies revealed amino acid residues 111–118 within the distal third C-terminus of KCNE1 as an important region. Insulin has direct electrophysiological effects on IKs currents, which may affect cardiac excitability. 相似文献
45.
Takeshi Nagamatsu Yuki Iwasawa‐Kawai Mayuko Ichikawa Kei Kawana Takahiro Yamashita Yutaka Osuga Tomoyuki Fujii Danny J. Schust 《American journal of reproductive immunology (New York, N.Y. : 1989)》2014,72(2):182-191
Recent progress in lipid research has unveiled new biologic roles for lysophospholipids as mediators of intercellular signaling. Lysophosphatidic acid (LPA) and sphingosine 1‐phosphate (S1P) are representative lysophospholipids. Accumulating evidence suggests that, acting as intercellular mediators, these and other lysophospholipids may play important roles in physiological and pathological situations. This review discusses the possible involvement of LPA and S1P in reproductive processes, with a focus on the regulatory mechanisms of pregnancy maintenance. As LPA promotes prostaglandin synthesis, mediators in the LPA pathway may also play a significant role in implantation and parturition. S1P signaling is thought to be essential in vascular formation within the uteroplacental unit and in fetomaternal immunologic interactions. Derangements in either one of these lysophospholipid signaling pathways could result in pregnancy complications that may include implantation failure, preeclampsia, and preterm labor. 相似文献
46.
Michinori Ogura Kiyoshi Ando Tatsuya Suzuki Kenichi Ishizawa Sung Yong Oh Kuniaki Itoh Kazuhito Yamamoto Wing Yan Au Hwei‐Fang Tien Yoshihiro Matsuno Takashi Terauchi Keiko Yamamoto Masahiko Mori Yoshinobu Tanaka Takashi Shimamoto Kensei Tobinai Won Seog Kim 《British journal of haematology》2014,165(6):768-776
Although initial rituximab‐containing chemotherapies achieve high response rates, indolent B‐cell non‐Hodgkin lymphoma (B‐NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B‐NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21‐d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression‐free survival (PFS). Fifty‐six eligible patients were enrolled; 50 patients (39 with FL, seven with other B‐NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab‐containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted. 相似文献
47.
Ohta Shin Tanaka Akihiko Jinno Megumi Hirai Kuniaki Miyata Yoshito Yamaguchi Munehiro Homma Tetsuya Muramoto Mayumi Watanabe Yoshio Suzuki Shintaro Yokoe Takuya Sagara Hironori 《Sleep & breathing》2020,24(2):523-532
Sleep and Breathing - Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity.... 相似文献
48.
S Makita T Onoda M Ohsawa F Tanaka T Segawa T Takahashi K Satoh K Itai K Tanno K Sakata S Omama Y Yoshida Y Ishibashi T Koyama T Kuribayashi K Ogasawara A Ogawa A Okayama M Nakamura 《Atherosclerosis》2012,224(1):222-227
Background and methodsThere is controversy about the association between mild-to-moderate alcohol consumption and a reduced risk of cardiovascular diseases. The relationships between daily alcohol consumption and the incidence of acute myocardial infarction (MI) or ischemic stroke (IS) were examined in men in a community-based, prospective cohort study (n = 8014, age 40–80 years, mean age = 64.1 years). Alcohol consumption was categorized into 3 groups (A1, none or occasional; A2, ≤25 g/day; A3, >25 g/day as ethanol) at baseline.ResultsDuring the mean follow-up of 5.5 years, 53 MIs and 186 ISs occurred. On Cox regression analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking index, and body mass index (BMI), the hazard ratio (HR) for incident MI was significantly lower in the A2 group than in the A1 group (HR = 0.49, p = 0.043). The HR for incident MI in the A3 group tended to be lower than in the A1 group (HR = 0.53, p = 0.10). In obese subjects, while a significantly lower HR for incident MI in the A2 group was retained (HR = 0.29, p = 0.049), no significant difference in the HR of the A3 group compared with the A1 group was found. No significant differences were found in the IS-free curve among the 3 groups of alcohol consumption.ConclusionsAlcohol consumption may have a protective effect on the onset of MI but not on IS in the general population. A U-shaped relation between alcohol consumption and incident MI was found in obese subjects. An appropriate limit for daily alcohol consumption, depending on the risk of ischemic heart disease, may need to be established. 相似文献
49.
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